Functional analysis of airway remodeling is related with fibrotic mediators in asthmatic children.

BACKGROUND: Asthmatic children present variable degrees of airway inflammation, remodeling, and resistance, which correlate with disease control and severity. The chronic inflammatory process of the airway triggers airway remodeling, which reflects the degree of airway resistance. Pro-inflammatory and pro-fibrotic mediators are centrally involved in this process. OBJECTIVE: To investigate whether the levels of pulmonary and systemic pro-inflammatory and pro-fibrotic mediators present a correlation with the resistance of the respiratory system and of the proximal and distal airways. METHODS: 39 Asthmatic children (persistent mild and moderate) and 39 non-asthmatic children (both between 6 and 13 years old) were evaluated for anthropometric characteristics, lung function and mechanics, and pulmonary and systemic immune responses. RESULTS: Asthmatic children showed an increased number of blood eosinophils (p < 0.04), basophils (p < 0.04), monocytes (p < 0.002) and lymphocytes (p < 0.03). In addition, asthmatic children showed impaired lung function, as demonstrated by FEV1 (p < 0.0005) and FEV1/FVC (p < 0.004), decreased total resistance of the respiratory system (R5Hz; p < 0.009), increased resistance of the proximal airways (R20Hz; p < 0.02), increased elastance (Z5Hz; p < 0.02) and increased reactance (X5Hz; p < 0.002) compared to non-asthmatic children. Moreover, the following inflammatory factors were significantly higher in asthmatic than non-asthmatic children: GM-CSF in the breath condensate (BC) (p < 0.0001) and in the serum (p < 0.0001); TGF-beta in the BC (p < 0.0001) and in the serum (p < 0.004); IL-5 in the BC (p < 0.02) and in the serum (p < 0.01); IL-4 in the serum (p < 0.0002). CONCLUSIONS: Impulse oscillometry is a sensitive method to detect airway resistance in persistent mild and moderate asthmatic children, an event followed by increased levels of pro-inflammatory and pro-fibrotic mediators.

Aerobic physical training reduces severe asthma phenotype involving kinins pathway.

INTRODUCTION: Aerobic physical training (APT) reduces eosinophilic airway inflammation, but its effects and mechanisms in severe asthma remain unknown. METHODS: An in vitro study employing key cells involved in the pathogenesis of severe asthma, such as freshly isolated human eosinophils, neutrophils, and bronchial epithelial cell lineage (BEAS-2B) and lung fibroblasts (MRC-5 cells), was conducted. Additionally, an in vivo study using male C57Bl/6 mice, including Control (Co; n = 10), Trained (Exe; n = 10), house dust mite (HDM; n = 10), and HDM + Trained (HDM + Exe; n = 10) groups, was carried out, with APT performed at moderate intensity, 5x/week, for 4 weeks. RESULTS: HDM and bradykinin, either alone or in combination, induced hyperactivation in human neutrophils, eosinophils, BEAS-2B, and MRC-5 cells. In contrast, IL-10, the primary anti-inflammatory molecule released during APT, inhibited these inflammatory effects, as evidenced by the suppression of numerous cytokines and reduced mRNA expression of the B1 receptor and ACE-2. The in vivo study demonstrated that APT decreased bronchoalveolar lavage levels of bradykinin, IL-1ß, IL-4, IL-5, IL-17, IL-33, TNF-α, and IL-13, while increasing levels of IL-10, klotho, and IL-1RA. APT reduced the accumulation of polymorphonuclear cells, lymphocytes, and macrophages in the peribronchial space, as well as collagen fiber accumulation, epithelial thickness, and mucus accumulation. Furthermore, APT lowered the expression of the B1 receptor and ACE-2 in lung tissue and reduced bradykinin levels in the lung tissue homogenate compared to the HDM group. It also improved airway resistance, tissue resistance, and tissue damping. On a systemic level, APT reduced total leukocytes, eosinophils, neutrophils, basophils, lymphocytes, and monocytes in the blood, as well as plasma levels of IL-1ß, IL-4, IL-5, IL-17, TNF-α, and IL-33, while elevating the levels of IL-10 and IL-1RA. CONCLUSION: These findings indicate that APT inhibits the severe asthma phenotype by targeting kinin signaling.

Three Main SCFAs Mitigate Lung Inflammation and Tissue Remodeling Nlrp3-Dependent in Murine HDM-Induced Neutrophilic Asthma.

Neutrophilic asthma is generally defined by poorly controlled symptoms and high levels of neutrophils in the lungs. Short-chain fatty acids (SCFAs) are proposed as nonpharmacological therapy for allergic asthma, but their impact on the neutrophilic asthma lacks evidence. SCFAs regulate immune cell responses and impact the inflammasome NLRP3, a potential pharmacological target for neutrophilic asthma. Here, we explored the capacity of SCFAs to mitigate murine-induced neutrophilic asthma and the contribution of NLRP3 to this asthma. The objective of this study is to analyze whether SCFAs can attenuate lung inflammation and tissue remodeling in murine neutrophilic asthma and NLRP3 contribution to this endotype. Wild-type (WT) C57BL6 mice orotracheally received 10 µg of HDM (house dust mite) in 80 µL of saline on days 0, 6-10. To explore SCFAs, each HDM group received 200 mM acetate, propionate, or butyrate. To explore NLRP3, Nlrp3 KO mice received the same protocol of HDM. On the 14th day, after euthanasia, bronchoalveolar lavage fluid (BALF) and lungs were collected to evaluate cellularity, inflammatory cytokines, and tissue remodeling. HDM group had increased BALF neutrophil influx, TNF-α, IFN-γ, IL-17A, collagen deposition, and mucus secretion compared to control. SCFAs distinctively attenuate lung inflammation. Only features of tissue remodeling were Nlrp3-dependent such as collagen deposition, mucus secretion, active TGF-ß cytokine, and IMs CD206+. SCFAs greatly decreased inflammatory cytokines and tissue remodeling. Only tissue remodeling was dependent on NLRP3. It reveals the potential of SCFAs to act as an additional therapy to mitigate neutrophilic asthma and the NLRP3 contribution to asthma.

Vitamin C Inhibits Lipopolysaccharide-Induced Hyperinflammatory State of Chronic Myeloid Leukemia Cells through Purinergic Signaling and Autophagy.

Background: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the overproduction of white blood cells, leading to symptoms such as fatigue, infections, and other complications. CML patients must take measures to prevent infections to mitigate the exacerbation of cancer cell proliferation and comorbidities. Methods: This study investigated whether vitamin C can suppress the hyperinflammatory activation of K-562 cells induced by lipopolysaccharide (LPS) and whether purinergic signaling (ATP and P2X7 receptor) and autophagy play a role in it. Two different doses of vitamin C (5 µg/mL and 10 µg/mL) were employed, along with the lysosome inhibitor chloroquine (CQ; 100 µM), administered 2 h prior to LPS stimulation (10 ng/mL) for a duration of 22 h in K-562 cells (3 × 105 cells/mL/well). Results: Both doses of vitamin C reduced the release of interleukin-6 (IL-6) (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01) and tumor necrosis factor (TNF) (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01) induced by LPS. Furthermore, in LPS + CQ-stimulated cells, vitamin C at a concentration of 10 µg/mL inhibited the expression of LC3-II (p < 0.05). Conversely, both doses of vitamin C led to the release of the anti-inflammatory cytokine interleukin-10 (IL-10) (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01), while only the 10 µg/mL dose of vitamin C induced the release of Klotho (10 µg/mL, p < 0.01). In addition, both doses of vitamin C reduced the accumulation of ATP (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01) and decreased the expression of the P2X7 receptor at the mRNA level. Conclusions: Vitamin C inhibits the hyperinflammatory state induced by LPS in K-562 cells, primarily by inhibiting the ATP accumulation, P2X7 receptor expression, and autophagy signaling.

Regular Practice of Physical Activity Improves Cholesterol Transfers to High-Density Lipoprotein (HDL) and Other HDL Metabolic Parameters in Older Adults.

The effects of regular physical activity on two important anti-atherosclerosis functions of high-density lipoprotein (HDL), namely its capacity to receive both forms of cholesterol and its anti-oxidant function, were investigated in this study comparing older adults with young individuals. One-hundred and eight healthy adult individuals were enrolled and separated into the following groups: active older (60-80 yrs, n = 24); inactive older (60-79 yrs, n = 21); active young (20-34 yrs, n = 39); and inactive young (20-35 yrs, n = 24). All performed cardiopulmonary tests. Blood samples were collected in order to assess the following measures: lipid profile, HDL anti-oxidant capacity, paraoxonase-1 activity, HDL subfractions, and lipid transfer to HDL. Comparing active older and active young groups with inactive older and inactive young groups, respectively, the active groups presented higher HDL-C levels (p < 0.01 for both comparisons), unesterified cholesterol transfer (p < 0.01, p < 0.05), and intermediate and larger HDL subfractions (p < 0.001, p < 0.01) than the respective inactive groups. In addition, the active young group showed higher esterified cholesterol transfer than the inactive young group (p < 0.05). As expected, the two active groups had higher VO2peak than the inactive groups; VO2peak was higher in the two younger than in the two older groups (p < 0.05). No differences in unesterified and esterified cholesterol transfers and HDL subfractions were found between active young and active older groups. HDL anti-oxidant capacity and paraoxonase-1 activity were equal in all four study groups. Our data highlight and strengthen the benefits of regular practice of physical activity on an important HDL function, the capacity of HDL to receive cholesterol, despite the age-dependent decrease in VO2peak.

Roux-en-Y Gastric Bypass Improves Adiponectin to Leptin Ratio and Inflammatory Profile in Severely Obese Women with and without Metabolic Syndrome: A Randomized Controlled Trial.

Obesity is a troubling public health problem as it increases risks of sleep disorders, respiratory complications, systemic arterial hypertension, cardiovascular diseases, type 2 diabetes mellitus, and metabolic syndrome (MetS). As a measure to counteract comorbidities associated with severe obesity, bariatric surgery stands out. This study aimed to investigate the adiponectin/leptin ratio in women with severe obesity with and without MetS who had undergone Roux-en-Y gastric bypass (RYGB) and to characterize the biochemical, glucose, and inflammatory parameters of blood in women with severe obesity before and after RYGB. Were enrolled females with severe obesity undergoing RYGP with MetS (n = 11) and without (n = 39). Anthropometric data and circulating levels of glucose, total cholesterol, high-density lipoprotein (HDL), non-HDL total cholesterol, low-density lipoprotein (LDL), adiponectin, and leptin were assessed before and 6 months after RYGB. Significant reductions in weight, body mass index, and glucose, total cholesterol, LDL, and leptin were observed after surgery, with higher levels of HDL, adiponectin, and adiponectin/leptin ratio being observed after surgery compared to the preoperative values of those. This study demonstrated that weight loss induced by RYGB in patients with severe obesity with or without MetS improved biochemical and systemic inflammatory parameters, particularly the adiponectin/leptin ratio.

Older Adults Who Maintained a Regular Physical Exercise Routine before the Pandemic Show Better Immune Response to Vaccination for COVID-19.

BACKGROUND: In this study, we aimed to investigate the specific-antibody response to the COVID-19 vaccination and the immunophenotyping of T cells in older adults who were engaged or not in an exercise training program before the pandemic. METHODS: Ninety-three aged individuals (aged between 60 and 85 years) were separated into 3 groups: practitioners of physical exercise vaccinated with CoronaVac (PE-Co, n = 46), or vaccinated with ChadOx-1 (PE-Ch, n = 23), and non-practitioners vaccinated with ChadOx-1 (NPE-Ch, n = 24). Blood samples were collected before (pre) and 30 days after vaccination with the second vaccine dose. RESULTS: Higher IgG levels and immunogenicity were found in the PE-Ch and NPE-Ch groups, whereas increased IgA levels were found only in the PE-Ch group post-vaccination. The PE-Co group showed a positive correlation between the IgA and IgG values, and lower IgG levels post-vaccination were associated with age. Significant alterations in the percentage of naive (CD28+CD57-), double-positive (CD28+CD57+), and senescent (CD28-CD57+) CD4+ T and CD8+ T cells were found post-vaccination, particularly in the PE-Ch group. CONCLUSIONS: The volunteers vaccinated with the ChadOx-1 presented not only a better antibody response but also a significant modulation in the percentage of T cell profiles, mainly in the previously exercised group.

Effects of Roux-en-Y gastric bypass on the metabolic profile and systemic inflammatory status of women with metabolic syndrome: randomized controlled clinical trial.

BACKGROUND: Obesity remains a public health problem worldwide. The high prevalence of this condition in the population raises further concerns, considering that comorbidities are often associated with obesity. Among the comorbidities closely associated with obesity, metabolic syndrome (MS) is particularly important, which potentially increases the risk of manifestation of other disorders, such as the prothrombotic and systemic pro-inflammatory states. METHODS: A randomized, controlled clinical trial was performed involving female patients (n = 32) aged between 18 and 65 years, with a clinical diagnosis of MS, with severe obesity undergoing Roux-en-Y gastric bypass (RYGB). The study design followed the Consolidated Standards of Reporting Trials statement (CONSORT). Lipid profile, blood glucose and adipokines (adiponectin, leptin, and resistin) and (cytokines IL-1ß, IL-6, IL-17, IL-23, and TNF-α) in blood plasma samples were evaluated before and six months after RYGB. RESULTS: Patients undergoing RYGB (BSG) showed a significant improvement from preoperative grade III obesity to postoperative grade I obesity. The results showed that while HDL levels increased, the other parameters showed a significant reduction in their postoperative values when compared not only to the values observed before surgery in the BSG group, but also to the values obtained in the control group (CG). As for systemic inflammatory markers adiponectin, leptin, resistin, IL-1ß, IL-6, IL-17, IL-23 and TNF- α it was observed that the levels of resistin and IL-17 in the second evaluation increased significantly when compared to the levels observed in the first evaluation in the CG. In the BSG group, while the levels of adiponectin increased, the levels of the other markers showed significant reductions in the postoperative period, in relation to the respective preoperative levels. The analysis of Spearman's correlation coefficient showed a significant positive correlation between IL-17 and IL-23 in the preoperative period, significant positive correlations between TNF-α and IL-6, TNF-α and IL-17, IL-6 and IL-17, and IL-17 and IL-23 were observed postoperatively. CONCLUSIONS: According to our results, the reduction of anthropometric measurements induced by RYGB, significantly improves not only the plasma biochemical parameters (lipid profile and glycemia), but also the systemic inflammatory status of severely obese patients with MS. Trials registration NCT02409160.

A phytotherapic blend immunity-6™ inhibits myeloid leukemic cells 2 activation involving purinergic signaling.

Leukemia is among the most common types of hematological cancers and the use of herbal medicines to prevent and treat leukemia are under quick development. Among several molecular pathways involved in leukemia pathogenesis and exacerbations, purinergic signaling is revealed as a key component. In the present study, the effects of two doses (5 ug/mL and 10 ug/mL) of Immunity-6™, a phytocomplex composed by beta-glucan, green tea (Camelia sinensis), chamomile (Matricaria chamomilla), and ascorbic acid (vitamin C) was tested in vitro, using chronic myelogenous leukemia cell line (K-562; 5 ×104/mL/well), which were challenged with lipopolysaccharide (LPS; 1 ug/mL) for 24 h. The results demonstrated that both doses of Immunity-6™ inhibited ATP release (p < 0.001) and P2×7 receptor at mRNA levels expression (p < 0.001). Purinergic inhibition by Immunity-6™ was followed by reduced release of proinflammatory cytokines IL-1beta (p < 0.001) and IL-6 (p < 0.001), while only 5 ug/mL of Immunity-6™ reduced the release of TNF-alpha (p < 0.001). Beyond to inhibit the release of pro-inflammatory cytokines, both doses of Immunity-6™ induced the release of anti-inflammatory cytokine IL-10 (p < 0.001), while only the higher dose (10 ug/mL) of Immunity-6™ induced the release of anti-inflammatory IL-1ra (p < 0.05) and klotho (p < 0.001). Thus, Immunity-6™ may be a promising adjuvant in the treatment of leukemia and further clinical trials are guaranteed.

A Nutritional Blend Suppresses the Inflammatory Response from Bronchial Epithelial Cells Induced by SARS-CoV-2.

Even after virus elimination, numerous sequelae of coronavirus disease 2019 (COVID-19) persist. Based on accumulating evidence, large amounts of proinflammatory cytokines are released to drive COVID-19 progression, severity, and mortality, and their levels remain elevated after the acute phase of COVID-19, playing a central role in the disease' sequelae. In this manner, bronchial epithelial cells are the first cells hyperactivated by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leading to massive cytokine release, triggering the hyperactivation of leukocytes and other cells, and mediating COVID-19 sequelae. Therefore, proinflammatory cytokine production is initiated by the host. This in vitro study tested the hypothesis that ImmuneRecov™, a nutritional blend, inhibits the SARS-CoV-2-induced hyperactivation of human bronchial epithelial cells (BEAS-2B). BEAS-2B (5x104/mL/well) cells were cocultivated with 1 ml of blood from a SARS-CoV-2-infected patient for 4 h, and the nutritional blend (1 µg/mL) was added in the first minute of coculture. After 4 h, the cells were recovered and used for analyses of cytotoxicity with the (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) (MTT) assay and the expression of the IL-1ß, IL-6, and IL-10 mRNAs. The supernatant was collected to measure cytokine levels. SARS-CoV-2 incubation resulted in increased levels of IL-1ß and IL-6 in BEAS-2B cells (p < 0.001). Treatment with the nutritional blend resulted in reduced levels of the proinflammatory cytokines IL-1ß and IL-6 (p < 0.001) and increased levels of the anti-inflammatory cytokine IL-10 (p < 0.001). Additionally, the nutritional blend reduced the expression of the IL-1ß and IL-6 mRNAs in SARS-CoV-2-stimulated cells and increased the expression of the IL-10 and IFN-γ mRNAs. In conclusion, the nutritional blend exerts important anti-inflammatory effects on cells in the context of SARS-CoV-2 infection.

Early mobilization in intensive care unit in Latin America: A survey based on clinical practice.

Background: The application of early mobilization (EM) in intensive care units (ICUs) has shown to improve the physical and ventilatory status of critically ill patients, even after ICU stay. This study aimed to describe the practices regarding EM in ICUs in Latin America. Methods: We conducted an observational, cross-sectional study of professionals from all countries in Latin America. Over 3 months, professionals working in ICU units in Latin America were invited to answer the survey, which was designed by an expert committee and incorporated preliminary questions based on studies about EM recommendations. Results: As many as 174 health professionals from 17 countries completed the survey. The interventions carried out within each ICU were active mobilization (90.5%), passive mobilization (85.0%), manual and instrumental techniques for drainage of mucus secretion (81.8%), and positioning techniques (81%). The professionals who most participated in the rehabilitation process in ICUs were physiotherapists (98.7%), intensive care physicians (61.6%), nurses (56.1%), and respiratory therapists (43.8%). In only 36.1% of the ICUs, protocols were established to determine when a patient should begin EM. In 38.1% of the cases, the onset of EM was established by individual evaluation, and in 25.0% of the cases, it was the medical indication to start rehabilitation and EM. Conclusion: This report shows us that EM of critically ill patients is an established practice in our ICUs like in other developed countries.

Hydrolyzed Collagen Induces an Anti-Inflammatory Response That Induces Proliferation of Skin Fibroblast and Keratinocytes.

Collagen-based products are found in different pharmaceuticals, medicine, food, and cosmetics products for a wide variety of applications. However, its use to prevent or improve the health of skin is growing dizzyingly. Therefore, this study investigated whether collagen peptides could induce fibroblast and keratinocyte proliferation and activation beyond reducing an inflammatory response induced by lipopolysaccharide (LPS). Human skin fibroblasts (CCD-1072Sk) and human keratinocytes (hKT-nh-skp-KT0026) were seeded at a concentration of 5 × 104 cells/mL. LPS (10 ng/mL) and three doses of collagen peptides (2.5 mg/mL, 5 mg/mL, 10 mg/mL) were used. The readout parameters were cell proliferation; expression of inducible nitric oxide synthase (iNOS); expression of pro-collagen-1α by fibroblasts; and secretion of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor α (TNF-α), transforming growth factor ß (TGF-ß), and vascular endothelial growth factor (VEGF) by both cell types. The results demonstrated that all doses of collagen supplementation induced increased proliferation of both human fibroblasts (p < 0.01) and human keratinocytes (p < 0.001), while only the dose of 10 mg/mL induced an increased expression of pro-collagen-1α by fibroblasts. Similarly, only the dose of 10 mg/mL reduced LPS-induced iNOS expression in fibroblasts (p < 0.05) and keratinocytes (p < 0.01). In addition, collagen supplementation reduced the LPS-induced IL-1ß (p < 0.05), IL-6 (p < 0.001), IL-8 (p < 0.01), and TNF-α (p < 0.05), and increased the TGF-ß and VEGF expression in fibroblasts. Furthermore, collagen supplementation reduced the LPS-induced IL-1ß (p < 0.01), IL-6 (p < 0.01), IL-8 (p < 0.01), and TNF-α (p < 0.001), and increased the TGF-ß (p < 0.05) and VEGF (p < 0.05) expression in keratinocytes. In conclusion, collagen peptides were found to induce fibroblast and keratinocyte proliferation and pro-collagen-1α expression, involving increased expression of TGF-ß and VEGF, as well as the suppression of an inflammatory response induced by LPS.

Physical Training Reduces Chronic Airway Inflammation and Mediators of Remodeling in Asthma.

Several benefits of aerobic training for asthmatic patients have been demonstrated. However, its effects on systemic inflammation and on airway remodeling mediators and lung mechanics are unknown. This prospective study included 21 intermittent and mild asthma patients, and as primary outcomes, the evaluation of pro- and anti-inflammatory and pro- and antifibrotic mediators in exhaled breath condensate (EBC) and blood were performed, beyond the cell counting in blood and in induced sputum. Aerobic training was performed for 3 months, 3 times per week. Aerobic training increased the levels of anti-inflammatory cytokines and of antifibrotic mediators in the breath condensate: IL-1ra (p = 0.0488), IL-10 (p = 0.0048), relaxin-3 (p = 0.0019), and klotho (p < 0.0043), respectively. Similarly, in plasma, increased levels of IL-1ra (p = 0.0147), IL-10 (p < 0.0001), relaxin-3 (p = 0.004), and klotho (p = 0.0023) were found. On contrary, reduced levels of proinflammatory cytokines in the breath condensate, IL-1ß (p = 0.0008), IL-4 (p = 0.0481), IL-5 (p < 0.0001), IL-6 (p = 0.0032), IL-13 (p = 0.0013), and TNF-α (p = 0.0001) and profibrotic markers VEGF (p = 0.0017) and TSLP (p = 0.0056) were found. Similarly, in plasma, aerobic training significantly reduced the levels of proinflammatory cytokines IL-1ß (p = 0.0008), IL-4 (p = 0.0104), IL-5 (p = 0.0001), IL-6 (p = 0.006), IL-13 (p = 0.0341), and TNF-α (p = 0.0003) and of profibrotic markers VEGF (p = 0.0009) and TSLP (p < 0.0076). Fractional exhaled nitric oxide (FeNO) was reduced after the intervention (p = 0.0313). Regarding inflammatory cells in sputum, there was a reduction in total cells (p = 0.008), eosinophils (p = 0.009), and macrophages (p = 0.020), as well as of blood eosinophils (p = 0.0203) and lymphocytes (p = 0.0198). Aerobic training positively modulates chronic airway inflammation and remodeling mediators, beyond to improve systemic inflammation in intermittent and mild asthmatic patients.

Combined resistance and aerobic training improves lung function and mechanics and fibrotic biomarkers in overweight and obese women.

Background: Obesity impairs lung function and mechanics and leads to low-grade inflammation, but the effects of combined physical exercise (CPE) on that are unknown. Methods: We investigated the effects of 12 weeks of combined physical exercise (aerobic + resistance training), in non-obese (n = 12), overweight (n = 17), and obese grade I (n = 11) women. Lung function and lung mechanics were evaluated. The systemic immune response was evaluated by whole blood analysis and biomarker measurements, while pulmonary fibrotic biomarkers were evaluated in the breath condensate. Result: CPE improved forced vital capacity (FVC) % (p < 0.001) and peak expiratory flow (PEF) % (p < 0.0003) in the obese group; resistance of the respiratory system (R5Hz) in non-obese (p < 0.0099), overweight (p < 0.0005), and obese (p < 0.0001) groups; resistance of proximal airways (R20Hz) in non-obese (p < 0.01), overweight (p < 0.0009), and obese (p < 0.0001) groups; resistance of distal airways (R5Hz-R20Hz) in non-obese (p < 0.01), overweight (p < 0.0012), and obese (p < 0.0001) groups; reactance of the respiratory system (X5Hz) in non-obese (p < 0.01), overweight (p < 0.0006), and obese (p < 0.0005) groups; impedance of the respiratory system (Z5Hz) in non-obese (p < 0.0099), overweight (p < 0.0005), and obese (p < 0.0001) groups; central resistance (RCentral) in non-obese (p < 0.01), overweight (p < 0.001), and obese (p < 0.0003) groups; and the peripheral resistance (RPeripheral) in non-obese (p < 0.03), overweight (p < 0.001), and obese (p < 0.0002) groups. CPE reduced the pro-fibrotic IGF-1 levels in BC in overweight (p < 0.0094) and obese groups (p < 0.0001) and increased anti-fibrotic Klotho levels in BC in obese (p < 0.0001) groups, and reduced levels of exhaled nitric oxide in overweight (p < 0.03) and obese (p < 0.0001) groups. Conclusion: CPE improves lung function, mechanics, and pulmonary immune response in overweight and obese grade I women by increasing anti-fibrotic protein Klotho and reducing pro-fibrotic IGF-1.

Distinct Immunological Profiles Help in the Maintenance of Salivary Secretory IgA Production in Mild Symptoms COVID-19 Patients.

Background: Relevant aspects regarding the SARS-CoV-2 pathogenesis and the systemic immune response to this infection have been reported. However, the mucosal immune response of the upper airways two months after SARS-CoV-2 infection in patients with mild/moderate symptoms is still not completely described. Therefore, we investigated the immune/inflammatory responses of the mucosa of the upper airways of mild/moderate symptom COVID-19 patients two months after the SARS-CoV-2 infection in comparison to a control group composed of non-COVID-19 healthy individuals. Methods: A cohort of 80 volunteers (age 37.2 ± 8.2), including non-COVID-19 healthy individuals (n=24) and COVID-19 patients (n=56) who presented mild/moderate symptoms during a COVID-19 outbreak in Brazil in November and December of 2020. Saliva samples were obtained two months after the COVID-19 diagnosis to assess the levels of SIgA by ELISA and the cytokines by multiplex analysis. Results: Salivary levels of SIgA were detected in 39 volunteers into the COVID-19 group and, unexpectedly, in 14 volunteers in the control group. Based on this observation, we distributed the volunteers of the control group into without SIgA or with SIgA sub-groups, and COVID-19 group into without SIgA or with SIgA sub-groups. Individuals with SIgA showed higher levels of IL-10, IL-17A, IFN-γ, IL-12p70, IL-13, and IFN-α than those without SIgA. In intergroup analysis, the COVID-19 groups showed higher salivary levels of IL-10, IL-13, IL-17A, and IFN-α than the control group. No statistical differences were verified in the salivary levels of IL-6 and IFN-ß. Lower IL-12p70/IL-10 and IFN-γ/IL-10 ratios were found in the control group without SIgA than the control group with SIgA and the COVID-19 group with SIgA. Conclusion: We were able to present, for the first time, that associations between distinct immunological profiles can help the mucosal immunity to maintain the salivary levels of SIgA in COVID-19 patients two months after the SARS-CoV-2 infection.

Provision of pulmonary rehabilitation in Latin America 18 months after the COVID-19 pandemic: A survey of the Latin American Thoracic Association.

INTRODUCTION: The Coronavirus disease (COVID-19) pandemic has significantly altered the provision of rehabilitation services, especially pulmonary rehabilitation (PR). Our objective was to assess the provision of PR services in Latin America 18 months after the COVID-19 pandemic was declared. METHODS: A cross-sectional study that included professionals dedicated to PR in centres in Latin America was applied. Responses to an online questionnaire were collected from May to September 2021. The following data were included for the analysis: demographic data, evaluation strategies, program structure, PR intervention in post-COVID-19 patients, and perception of strategies therapies for the care of post-COVID-19 patients. The questionnaire was distributed in Spanish and Portuguese languages. RESULTS: Responses were received from 196 PR centres. Exercise tolerance was predominantly measured with the six-minute walk test. Less than 50% of the institutions evaluate quality of life, physical qualities, symptoms, and lung function. Most of the programmes have physiotherapists (90.8%), as well as pulmonologists (60%), and psychologists (35%), among other professionals. CONCLUSION: PR services in Latin America have adapted in their way to the requirements of the pandemic, and most continued to provide face-to-face services. It was identified that the application of the programs is heterogeneous both in evaluations and interventions.

Lacticaseibacillus rhamnosus modulates the inflammatory response and the subsequent lung damage in a murine model of acute lung inflammation.

OBJECTIVE: The present study investigated the anti-inflammatory effect of the probiotic Lacticaseibacillus rhamnosus (Lr) on lung inflammation induced by Lipopolysaccharide (LPS) of Escherichia coli in C57BL/6 mice. METHODS: C57BL/6 mice were divided into four groups: control, LPS, Lr (1 day) + LPS, and Lr (14 days) + LPS. Total and differential cells from Bronchoalveolar Lavage Fluid (BALF) were counted in a Neubauer 40X chamber, and pro-and anti-inflammatory cytokines (IL-1ß, IL-6, CXCL-1, TNF-α, TGF-ß, and IL-10) were measured by ELISA assay. The analysis of whole leukocytes in blood was performed using the automated system Sysmex 800i. Morphometry of pulmonary tissue evaluated alveolar hemorrhage, alveolar collapse, and inflammatory cells. Pulmonary vascular permeability was assessed by Evans blue dye extravasation, and bronchoconstriction was evaluated in a tissue bath station. The transcription factor NF-kB was evaluated by ELISA, and its gene expression and TLR-2, TLR-4, MMP-9, MMP-12, and TIMP by PCR. RESULTS: The probiotic Lr had a protective effect against the inflammatory responses induced by LPS. Lr significantly reduced pro-inflammatory cells in the airways, lung parenchyma, and blood leukocytes. Furthermore, Lr reduced the production of pro-inflammatory cytokines and chemokines in BALF and the expression of TLRs, MMPs, and NF-kB in lung tissue and maintained the expression of TIMP in treated animals promoting a protective effect on lung tissue. CONCLUSIONS: The results of the study indicate that pre-treatment with the probiotic Lr may be a promising way to mitigate lung inflammation in endotoxemia.

MiodesinTM Positively Modulates the Immune Response in Endometrial and Vaginal Cells.

Endometriosis presents high prevalence and its physiopathology involves hyperactivation of endometrial and vaginal cells, especially by bacteria. The disease has no cure and therapies aiming to inhibit its development are highly desirable. Therefore, this study investigated whether MiodesinTM (10 µg/mL = IC80; 200 µg/mL = IC50), a natural compound constituted by Uncaria tomentosa, Endopleura uchi, and astaxanthin, could exert anti-inflammatory and anti-proliferative effects against Lipopolysaccharides (LPS) stimulation in endometrial and Candida albicans vaginal cell lines. VK2 E6/E7 (vaginal) and KLE (epithelial) cell lines were stimulated with Candida albicans (1 × 107 to 5 × 107/mL) and LPS (1 µg/mL), respectively. MiodesinTM inhibited mRNA expression for Nuclear factor kappa B (NF-κB), ciclo-oxigenase 1 (COX-1), and phospholipase A2 (PLA2), beyond the C-C motif chemokine ligand 2 (CCL2), CCL3, and CCL5 in VK2 E6/E7 cells (p < 0.05). In addition, the inhibitory effects of both doses of MiodesinTM (10 µg/mL and 200 µg/mL) resulted in reduced secretion of interleukin-1ß (IL-1ß), IL-6, IL-8, tumor necrosis factor α (TNF-α) (24 h, 48 h, and 72 h) and CCL2, CCL3, and CLL5 (p < 0.05) by VK2 E6/E7 cells. In the same way, COX-1 MiodesinTM inhibited LPS-induced hyperactivation of KLE cells, as demonstrated by reduced secretion of IL-1ß, IL-6, IL-8, TNF-α (24 h, 48 h, and 72 h) and CCL2, CCL3, and CLL5 (p < 0.05). Furthermore, MiodesinTM also inhibited mRNA expression and secretion of matrix metalloproteinase-2 (MMP-2), MMP-9, and vascular endothelial growth factor (VEGF), which are key regulators of invasion of endometrial cells. Thus, the study concludes that MiodesinTM presents beneficial effects in the context of endometriosis, positively affecting the inflammatory and proliferative response.

Moderate Treadmill Training Induces Limited Effects on Quadriceps Muscle Hypertrophy in Mice Exposed to Cigarette Smoke Involving Metalloproteinase 2.

BACKGROUND: Long-term cigarette smoke (CS) induces substantive extrapulmonary effects, including musculoskeletal system disorders. Exercise training seems to protect long-term smokers against fiber atrophy in the locomotor muscles. Nevertheless, the extracellular matrix (ECM) changes in response to aerobic training remain largely unknown. Thus, we investigated the effects of moderate treadmill training on aerobic performance, cross-sectional area (CSA), fiber distribution, and metalloproteinase 2 (MMP-2) activity on quadriceps muscle in mice exposed to chronic CS. METHODS: Male mice were randomized into four groups: control or smoke (6 per group) and exercise or exercise+smoke (5 per group). Animals were exposed to 12 commercially filtered cigarettes per day (0.8 mg of nicotine, 10 mg of tar, and 10 mg of CO per cigarette). The CSA, fibers distribution, and MMP-2 activity by zymography were assessed after a period of treadmill training (50% of maximal exercise capacity for 60 min/day, 5 days/week) for 24 weeks. RESULTS: The CS exposure did not change CSA compared to the control group (p>0.05), but minor fibers in the frequency distribution (<1000 µm2) were observed. Long-term CS exposure attenuated CSA increases in exercise conditions (smoke+exercise vs exercise) while did not impair aerobic performance. Quadriceps CSA increased in mice nonsmoker submitted to aerobic training (p = 0.001). There was higher pro-MMP-2 activity in the smoke+exercise group when compared to the smoke group (p = 0.01). Regarding active MMP-2, the exercise showed higher values when compared to the control group (p = 0.001). CONCLUSION: Moderate treadmill training for 24 weeks in mice exposed to CS did not modify CSA, despite inducing higher pro-MMP-2 activity in the quadriceps muscle, suggesting limited effects on ECM remodeling. Our findings may contribute to new insights into molecular mechanisms for CS conditions.